What is epcoritamab-bysp?
Epcoritamab-bysp is a humanized bispecific IgG1 antibody made from Chinese hamster ovary. It is a bispecific CD3 T-cell engager directed towards CD20, which is commonly expressed in B-cell malignancies. Epcoritamab-bysp binds to the CD3 receptor on T cells and to the CD20 receptors on B cells. Once it binds, T cells are activated causing B-cell death and release of cytokines.
What is epcoritamab-bysp approved for?
Epcoritamab-bysp is FDA-approved for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of therapy. Epcoritamab-bysp was studied in 157 patients with relapsed or refractory large B-cell lymphoma with a median of three prior lines of therapy, including 39 percent with prior chimeric antigen receptor T-cell therapy. Patients were excluded if they had central nervous system involvement. Over half (63%) achieved an overall response, with 40 percent achieving a complete response (CR). The median duration of CR was 21 months and median time to CR was 3 months. Estimated progression-free survival at 9, 12, and 15 months for those that achieved a CR was 91 percent, 87 percent, and 81 percent, respectively. Median overall survival (OS) was 19 months, and median OS was not reached in those that achieved a CR.
How do you administer this drug?
Epcoritamab-bysp is administered subcutaneously with weekly dose escalation. On Cycle 1 Day 1, a dose of 0.16 mg is administered. On Cycle 1 Day 8, the dose increases to 0.8 mg. On Cycle 1 Day 15 and Day 22, the patient receives the full dose of 48 mg. The patient then receives weekly injections of 48 mg during Cycles 2 and 3 (Day 1, 8, 15, and 22). During Cycles 4-9, epcoritamab-bysp is given on Days 1 and 15. For Cycles 10 and beyond, it is given only on Day 1 of each cycle. Cycles are approximately 28 days long and epcoritamab-bysp is administered until disease progression or unacceptable toxicity.
Are there any pre-medications needed?
All patients should receive prednisone 100 mg or dexamethasone 15 mg or equivalent (oral or intravenous) 30-120 minutes prior to all administrations during Cycle 1 and for 3 consecutive days after each administration. Diphenhydramine 50 mg and acetaminophen 650-1,000 mg should also be given 30-120 minutes prior to each weekly administration in Cycle 1. For subsequent cycles, patients who experienced prior Grade 2 or 3 cytokine release syndrome (CRS) should be pre-medicated with prednisone 100 mg or dexamethasone 15 mg or equivalent (oral or intravenous) 30-120 minutes prior to the next administration and for 3 consecutive days after until epcoritamab-bysp is given without any Grade 2 or greater CRS.
What are the side effects?
The most common adverse events (> or =20%) include CRS, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, diarrhea, bone marrow suppression, and electrolyte abnormalities.
Although uncommon (less than 20%), immune effector cell-associated neurotoxicity (ICANS), sepsis, pleural effusions, pneumonia, tumor flare, febrile neutropenia, and tumor lysis syndrome can occur. Edema, vomiting, rash, headache, decreased appetite, and cardiac arrythmias have also been reported.
Are there any important drug interactions?
There are no direct drug interactions known. Epcoritamab-bysp can cause cytokine release, which may suppress CYP enzyme activity and result in increased exposure to CYP substrates. This is most likely to occur in the first month of therapy when CRS is most prevalent.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
No dose adjustments are needed in patients with mild-to-moderate renal dysfunction or hepatic impairment. Epcoritamab-bysp was not studied in patients with severe renal or hepatic impairment.
What should my patients know about epcoritamab-bysp?
* CRS and ICANS are serious adverse effects and can be fatal. Patients should be instructed to contact their doctor or report to an emergency room if they experience fever, low blood pressure, shortness of breath, chills, rapid heart rate, confusion, lethargy, tremor, difficulty talking or swallowing, or seizures.
* Patients should be hospitalized for at least 24 hours after the Cycle 1 Day 15 dose to monitor for CRS.
* Epcoritamab-bysp can cause serious infection. Patients should contact their provider if they experience signs or symptoms of infection.
* Epcoritamab-bysp may cause fetal harm and should not be used in pregnancy or in women who are nursing. Contraception should be used during treatment and for 4 months after the last dose.
What else should I know about this drug?
* Patients should be given pneumocystis jirovecii pneumonia prophylaxis prior to starting treatment with epcoritamab-bysp. Herpes virus prophylaxis should be considered.
* Of patients that experienced CRS, the majority experienced it after the full dose on Cycle 1 Day 15. The median onset of CRS was 21 hours and the median duration was 2 days.
* Specific instructions on what to do if the dose is delayed during ramp-up can be found in the package insert.
What useful links are available regarding epcoritamab-bysp?
* Prescribing information: https://tinyurl.com/mrjdx59d
* FDA Approval: https://tinyurl.com/36aw2zxv
Are there any ongoing clinical trials related to epcoritamab-bysp?
Epcoritamab-bysp is also being studied as monotherapy and in combination with other agents in adult and pediatric patients with B-cell malignancies, including follicular lymphoma, chronic lymphocytic leukemia, or Richter's syndrome. More information is available about the trial at clinicaltrials.gov.
ALEXANDRA LOVELL, PharmD, BCOP, is Clinical Pharmacy Specialist in Leukemia at the University of Texas MD Anderson Cancer Center. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/Manager, Clinical Pharmacy Services at Washington University School of Medicine. She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, is Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine. He serves as the Pharmacy Forum column physician advisor.